Tags

Type your tag names separated by a space and hit enter

Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands.
Expert Opin Ther Pat. 2009 May; 19(5):593-606.EO

Abstract

BACKGROUND

The active form of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), plays an important role in calcium homeostasis, cell differentiation, cell proliferation and immunity. A more complete understanding of the several physiological and pharmacological properties of 1,25(OH)(2)D(3) indicates that the vitamin D receptor (VDR) is a promising drug target in the treatment of cancers, autoimmune diseases, infections and cardiovascular disease as well as bone and mineral disorders. The calcemic effect of 1,25(OH)(2)D(3) and its derivatives has limited their clinical application. As a result, the development of non-calcemic VDR ligands is required to realize the potential of VDR-targeting therapy.

OBJECTIVE

In this review, we discuss the in vitro and in vivo pharmacological actions, including VDR interaction, regulation of cofactor recruitment, pharmacokinetics and cell type or tissue-selective action of VDR ligands with less-calcemic activity.

CONCLUSION

Pharmacokinetic parameters and selective tissue accumulation are related to the therapeutic benefit of non-hypercalcemic vitamin D derivatives. Induction of distinct VDR conformations and cofactor recruitment may be associated with selective actions of non-secosteroidal VDR ligands. Derivatives of lithocholic acid, a newly identified endogenous VDR ligand, are less-calcemic VDR ligands.

Authors+Show Affiliations

Nihon University School of Medicine, Division of Biochemistry, Department of Biomedical Sciences, Tokyo, Japan.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19441936

Citation

Choi, Mihwa, and Makoto Makishima. "Therapeutic Applications for Novel Non-hypercalcemic Vitamin D Receptor Ligands." Expert Opinion On Therapeutic Patents, vol. 19, no. 5, 2009, pp. 593-606.
Choi M, Makishima M. Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands. Expert Opin Ther Pat. 2009;19(5):593-606.
Choi, M., & Makishima, M. (2009). Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands. Expert Opinion On Therapeutic Patents, 19(5), 593-606. https://doi.org/10.1517/13543770902877717
Choi M, Makishima M. Therapeutic Applications for Novel Non-hypercalcemic Vitamin D Receptor Ligands. Expert Opin Ther Pat. 2009;19(5):593-606. PubMed PMID: 19441936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic applications for novel non-hypercalcemic vitamin D receptor ligands. AU - Choi,Mihwa, AU - Makishima,Makoto, PY - 2009/5/16/entrez PY - 2009/5/16/pubmed PY - 2009/7/28/medline SP - 593 EP - 606 JF - Expert opinion on therapeutic patents JO - Expert Opin Ther Pat VL - 19 IS - 5 N2 - BACKGROUND: The active form of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), plays an important role in calcium homeostasis, cell differentiation, cell proliferation and immunity. A more complete understanding of the several physiological and pharmacological properties of 1,25(OH)(2)D(3) indicates that the vitamin D receptor (VDR) is a promising drug target in the treatment of cancers, autoimmune diseases, infections and cardiovascular disease as well as bone and mineral disorders. The calcemic effect of 1,25(OH)(2)D(3) and its derivatives has limited their clinical application. As a result, the development of non-calcemic VDR ligands is required to realize the potential of VDR-targeting therapy. OBJECTIVE: In this review, we discuss the in vitro and in vivo pharmacological actions, including VDR interaction, regulation of cofactor recruitment, pharmacokinetics and cell type or tissue-selective action of VDR ligands with less-calcemic activity. CONCLUSION: Pharmacokinetic parameters and selective tissue accumulation are related to the therapeutic benefit of non-hypercalcemic vitamin D derivatives. Induction of distinct VDR conformations and cofactor recruitment may be associated with selective actions of non-secosteroidal VDR ligands. Derivatives of lithocholic acid, a newly identified endogenous VDR ligand, are less-calcemic VDR ligands. SN - 1744-7674 UR - https://www.unboundmedicine.com/medline/citation/19441936/Therapeutic_applications_for_novel_non_hypercalcemic_vitamin_D_receptor_ligands_ L2 - http://www.tandfonline.com/doi/full/10.1517/13543770902877717 DB - PRIME DP - Unbound Medicine ER -